surotomycin and cadazolid

Clostridium difficile infections (CDI) remain a challenge to treat clinically due primarily to limited number of antibiotics available and unacceptably high recurrence rates. Because of this, there has been significant demand for creating innovative therapeutics, which has resulted in the development of several novel antibiotics.. This review updates seven different antibiotics that are currently in development to treat CDI including fidaxomicin, surotomycin, ridinilazole, ramoplanin, cadazolid, LFF571, and CRS3123. Available preclinical and clinical data are compared between these antibiotics.. Many of these new antibiotics display almost ideal properties for antibiotics directed against CDI. Despite these properties, not all clinical development of these compounds has been successful. These studies have provided key insights into the pathogenesis of CDI and will continue to inform future drug development. Successful phase III clinical trials should result in several new and novel antibiotics to treat CDI.

Topics: Anti-Bacterial Agents; Benzimidazoles; Benzopyrans; Clinical Trials as Topic; Clostridium Infections; Depsipeptides; Humans; Lipopeptides; Oxazolidinones; Peptides, Cyclic; Pyridines; Thiazoles; Thiophenes

Antibiotic development goals for CDI include potent antimicrobial effect against C. difficile, limited killing of host microbiota, potential effect on spores, and ability to interfere with toxin production. Cadazolid, a novel, non-absorbable hybrid antibiotic has many of these criteria. In phase I and II clinical trials, cadazolid was shown to be safe, well tolerated, and efficacious positioning itself as a potential future viable therapeutic option for CDI. Areas covered: This review provides an in-depth evaluation of the chemistry, microbiology, pharmacodynamics, pharmacokinetics, and clinical trial results for cadazolid. Clinical therapeutic outcomes are compared between cadazolid, fidaxomicin, and surotomycin. Expert opinion: Preclinical and early clinical studies demonstrated that cadazolid has unique properties that will likely be valuable to treat CDI and reduce recurrent infection. With compelling phase II clinical results, results from the ongoing phase III trial will better define the role of cadazolid for treating CDI in the future.

Topics: Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Fidaxomicin; Humans; Lipopeptides; Oxazolidinones; Peptides, Cyclic; Treatment Outcome

Clostridium difficile infection has attained high prominence given its prevalence and impacts on patients and healthcare institutions. Multiple new approaches to the prevention and treatment of C. difficile infection (CDI) are undergoing clinical trials.. Bezlotoxumab is a monoclonal antibody against toxin B that has successfully completed phase III studies, demonstrating a significant reduction in recurrent CDI when given with standard of care antibiotics. Antibiotics under development include cadazolid and ridinilazole, whereas surotomycin has had disappointing phase III results. Multiple live biotherapeutics are being developed, including freeze thawed and encapsulated versions of faecal microbiota transplantation to improve the practicality of treating patients with recurrent CDI. Alternatives to faecal microbiota transplantation, that aim to improve safety, including a microbial suspension, RBX2660, and a complex spore formulation, SER-109, have progressed to phase II studies. A nontoxigenic C. difficile strain has also shown promise to prevent recurrent CDI. In addition, three C. difficile vaccines have progressed to phase II/III clinical trials.. The diverse approaches to treating and preventing CDI offer substantial promise that new treatment options will soon emerge, particular ones that reduce the risk of recurrences.

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Antibodies, Neutralizing; Benzimidazoles; Broadly Neutralizing Antibodies; Clostridioides difficile; Clostridium Infections; Fecal Microbiota Transplantation; Humans; Lipopeptides; Oxazolidinones; Peptides, Cyclic; Pyridines; Recurrence; Secondary Prevention